Bioassay Guided Isolation and α-Glucosidase Inhibition Studies of a New Sesquiterpene from Ochradenus aucheri.

AIMS: The aim of the current study was to explore the anti-diabetic potential of Ochradenus aucheri Boiss (O. aucheri). METHOD: All the fractions of O. aucheri were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor. RESULTS: The preliminary screening showed that all the fractions including n-hexane (38.0 ± 1.38 µg/mL), dichloromethane (92.6 ± 6.18 µg/mL), ethyl acetate (29.2 ± 0.51 µg/mL) and n-butanol (361.8 ± 5.80 µg/mL) displayed significant α-glucosidase inhibitory activity. The activity-directed fractionation and purification of ethyl acetate fraction led to the isolation of one new sesquiterpenoid, Jardenol (1), and two known metabolites: ß-stitosterol-3-O-ß-D-glucopyranoside (2) and ß-Sitosterol (3). To the best of our knowledge, these metabolites have not been isolated from this plant previously. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. Compound 1 showed significant α-glucosidase inhibition with an IC50 value of 138.2 ± 2.43 µg/mL as compared to positive control acarbose (IC50 = 942.0 ± 0.60 µg/mL). Additionally, in-silico docking was employed to predict the binding mechanism of compound 1 in the active site of the target enzyme, α-glucosidase. The docking results suggested that the compound forms strong interactions at the catalytic site of α-glucosidase. CONCLUSION: The results of the present study indicated that the newly purified secondary metabolite, Jardenol, can be a promising anti-diabetic compound.

Synthesis, in vitro biological evaluation and in silico studies of novel pyrrolidine derived thiosemicarbazones as dihydrofolate reductase inhibitors.

Dihydrofolate reductase (DHFR) is a crucial enzyme involved in folate metabolism and serves as a prime target for anticancer and antimicrobial therapies. In this study, a series of 4-pyrrolidine-based thiosemicarbazones were synthesized and evaluated for their DHFR inhibitory activity. The synthesis involved a multistep procedure starting from readily available starting materials, leading to the formation of diverse thiosemicarbazone 5(a-r) derivatives. These compounds were then subjected to in vitro assays to evaluate their inhibitory potential against DHFR enzyme. The synthesized compounds 5(a-r) exhibited potent inhibition with IC50 values in the range of 12.37 ± 0.48 µM to 54.10 ± 0.72 µM. Among all the derivatives 5d displayed highest inhibitory activity. Furthermore, molecular docking and ADME studies were performed to understand the binding interactions between the synthesized compounds and the active site of DHFR. The in vitro and in silico data were correlated to identify compounds with promising inhibitory activity and favorable binding modes. This comprehensive study provides insights into the structure-activity relationships of 4-pyrrolidine-based thiosemicarbazones as DHFR inhibitors, offering potential candidates for further optimization towards the development of novel therapeutic agents.

Macrophage modulation with dipeptidyl peptidase-4 inhibitors: A new frontier for treating diabetic cardiomyopathy?

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy (DCM) treatment by dipeptidyl peptidase-4 (DPP-4) inhibitors. Zhang et al studied teneligliptin, a DPP-4 inhibitor used for diabetes management, and its potential cardioprotective effects in a diabetic mouse model. They suggested teneligliptin administration may reverse established markers of DCM, including cardiac hypertrophy and compromised function. It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice. Macrophages play crucial roles in DCM pathogenesis. Chronic hyperglycemia disturbs the balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages, favoring a pro-inflammatory state contributing to heart damage. Here, we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment. These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome. Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

Design, synthesis, and in vitro and in silico study of 1-benzyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors.

Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables. A novel series of N-1 and C-3 substituted indole-based thiosemicarbazones 5(a-r) are synthesized and further analyzed for their inhibition potential against tyrosinase enzyme through in vitro assays. The synthesized compounds displayed very good to moderate inhibition with half maximal inhibitory concentration in the range of 12.40 ± 0.26 µM to 47.24 ± 1.27 µM. Among all the derivatives 5k displayed the highest inhibitory activity. According to SAR analysis, the derivatives with 4-substitution at the benzyl or phenyl ring of the thiosemicarbazones exhibited better inhibitory potential against tyrosinase. In silico analysis (including ADMET prediction and molecular docking) was conducted and compared with the standard drug (kojic acid). These findings may help the hunt for new melanogenesis inhibitors that the food and cosmetics industries may find valuable.

Copper and nitrogen-doped carbon quantum dots as green nano-probes for fluorimetric determination of delafloxacin; characterization and applications.

BACKGROUND: Carbon quantum dots (CQDs) have gained much interest recently for being efficient probes. Their cost-effectiveness, eco-friendliness, and unique photocatalytic activities made them distinctive alternatives to other luminescent approaches like fluorescent dyes and luminous derivatization. Meanwhile, delafloxacin (DLF) is a recently approved antibacterial medicine. DLF has been authorized for the treatment of soft-tissue and skin infections as well as pneumonia. Therefore, new eco-friendly, cost-effective, and sensitive tools are needed its estimation in different matrices. RESULTS: In the proposed study, green copper and nitrogen carbon dots (Cu-N@CDs) were synthesized from a green source (plum juice with copper sulphate). Cu-N@CQDs were then characterized using multiple tools including X-ray photon spectroscopy (XPS), FTIR and UV-VIS spectroscopy, Zeta potential measurements, High-resolution transmission electron microscopy (HRTEM), and fluorescence spectroscopy. After gradually adding DLF, the developed quantum dots' fluorescence was significantly enhanced within the working range of 0.5-100.0 ng mL-1. The limits of detection and quantification were 0.08 and 0.27 ng mL-1, respectively. The accuracy of the proposed method ranged from 96.00 to 99.12 % in recovery%, when recovered from milk and plasma samples. SIGNIFICANCE: Cu-N@CDs were utilized and validated for selectively determining DLF in several matrices including pharmaceutical forms, human plasma and in milk samples using spectrofluorimetric technique. The bio-analytical method is simple and could be used in content uniformity testing as well as in therapeutic drug monitoring in human plasma.

Synthesis, in vitro and in silico study of novel 1,3-diphenylurea derived Schiff bases as competitive α-glucosidase inhibitors.

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 µM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase (K i = 3.96 ± 0.0048 µM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients.

Examining the potential of peppermint essential oil-infused pectin and kappa-carrageenan composite films for sustainable food packaging.

Essential oils are key ingredients in the development of edible films and provide a diverse approach to improving food preservation, as well as sensory qualities. The pectin and kappa-carrageenan composite films were obtained by adding peppermint essential oil in different quantities. The films after their fabrication were thoroughly evaluated for their attributes, which included mechanical, barrier, optical, chemical, thermal, and antioxidant properties. The visual assessment of the films demonstrated that PEO-loaded films showed a uniform, homogenous, and slightly yellowish appearance. There was an increase in the thickness (0.045 ± 0.006 to 0.060 ± 0.008 mm), elongation at break (12.73 ± 0.74 to 25.05 ± 1.33 %), and water vapor permeability (0.447 ± 0.014 to 0.643 ± 0.014 (g*mm)/(m2*h*kPa)) was observed with the addition of PEO. However, tensile strength (45.84 ± 3.69 to 29.80 ± 2.10 MPa) and moisture content (25.83 ± 0.046 to 21.82 ± 0.23 %) decreased with the incorporation of PEO. Furthermore, thermal and antioxidant properties were enhanced by the inclusion of PEO. The presented investigation can be employed to synthesize food packaging material with antioxidant properties with potential applications in food packaging.

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.

INTRODUCTION: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential. METHOD: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 µM. The derivative 5h, with an IC50 of 13.60 ± 2.51 µM, emerged as the most potent inhibitor. RESULTS: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results. CONCLUSION: All findings underscored the potential of synthesized derivatives for drug development.

Exploring the Therapeutic Potential of Coumarin-thiazolotriazole Pharmacophores for SARS-CoV-2 Spike Protein through In-vitro and In-silico Evaluation.

INTRODUCTION: The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally. METHOD: Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses. in vitro and in silico techniques were used in the current study to identify novel inhibitors of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles against the SARS-CoV-2 spike protein. RESULT: Interestingly, all the tested molecules demonstrated substantial inhibition of spike protein with 91.81-57.90% inhibition. The spike protein was remarkably inhibited by compounds 6k (91.83%), 6j (89.75%), 6m (87.69%),6i (86.60%), 6l (85.40%), 6h (84.70%), 6l (84.70%), 6g (83.40%), 6b (82.60%), 6f (81.90%), while compounds 6d 6a, 6c, and 6e exhibited significant activity against spike protein with 79.60%, 77.10%, 75.30%, and 57.90% inhibition, respectively. The binding mechanism of these novel inhibitors with spike protein was deduced in silico, which reflects that the active molecules firmly bind with the receptor binding domain (RBD) of spike protein, thereby inhibiting its function. CONCLUSION: The combined in vitro and in silico investigations unfold the therapeutic potential of coumarin-thiazolotriazole scaffolds in the treatment of SARS-CoV-2 infection.

Pioglitazone as a potential modulator in autoimmune diseases: a review on its effects in systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis.

INTRODUCTION: Current medications for autoimmune disorders often induce broad-ranging side effects, prompting a growing interest in therapies with more specific immune system modulation. Pioglitazone, known for its anti-diabetic properties, is increasingly recognized for significant immunomodulatory potential. Beyond its traditional use in diabetes management, pioglitazone emerges as a promising therapeutic candidate for autoimmune disorders. AREAS COVERED: This comprehensive review explores pioglitazone's impact on four prominent autoimmune conditions: systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. We focus on pioglitazone's diverse effects on immune cells and cytokines in these diseases, highlighting its potential as a valuable therapeutic option for autoimmune diseases. Here we have reviewed the latest and most current research literature available on PubMed, based on research published in the last 15 years. EXPERT OPINION: Pioglitazone as an immunomodulatory agent can regulate T cell differentiation, inhibit inflammatory cytokines, and promote anti-inflammatory macrophages. While further clinical studies are needed to fully understand its mechanisms and optimize treatment strategies, pioglitazone represents a potential therapeutic approach to improve outcomes for patients with these challenging autoimmune conditions. The future of autoimmune disease research may involve personalized treatment approaches, and collaborative efforts to improve patient quality of life.

This article explores the potential use of pioglitazone, a medication commonly used to treat diabetes, for autoimmune disorders treatment. The focus of the review centers around the effects of pioglitazone on systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. In the case of systemic lupus erythematosus, pioglitazone appears to induce a shift in specific immune cells, leading to a reduction in systemic inflammation and damage to organs. In psoriasis, the medication shows promise in suppressing immune responses, thereby alleviating skin inflammation. For individuals with inflammatory bowel disease, pioglitazone seems to safeguard a protein with anti-inflammatory properties, aiding in the repair of bowel tissue. Regarding multiple sclerosis, pioglitazone appears to influence the behavior of immune cells and promote the restoration of nerve tissue. These diverse effects of pioglitazone on the immune system suggest its potential as a valuable treatment option for autoimmune diseases. However, it is important to note that further research is necessary to fully comprehend the mechanisms by which pioglitazone operates and to determine the optimal approaches for its utilization in clinical studies.

Regulatory Dynamics of Plant Hormones and Transcription Factors under Salt Stress.

The negative impacts of soil salinization on ion homeostasis provide a significant global barrier to agricultural production and development. Plant physiology and biochemistry are severely affected by primary and secondary NaCl stress impacts, which damage cellular integrity, impair water uptake, and trigger physiological drought. Determining how transcriptional factors (TFs) and hormone networks are regulated in plants in response to salt stress is necessary for developing crops that tolerate salt. This study investigates the complex mechanisms of several significant TF families that influence plant responses to salt stress, involving AP2/ERF, bZIP, NAC, MYB, and WRKY. It demonstrates how these transcription factors (TFs) help plants respond to the detrimental effects of salinity by modulating gene expression through mechanisms including hormone signaling, osmotic stress pathway activation, and ion homeostasis. Additionally, it explores the hormonal imbalances triggered by salt stress, which entail complex interactions among phytohormones like jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA) within the hormonal regulatory networks. This review highlights the regulatory role of key transcription factors in salt-stress response, and their interaction with plant hormones is crucial for developing genome-edited crops that can enhance agricultural sustainability and address global food security challenges.

Design, synthesis, in vitro and in silico studies of novel piperidine derived thiosemicarbazones as inhibitors of dihydrofolate reductase.

Dihydrofolate reductase (DHFR), an essential enzyme in folate metabolism, presents a promising target for drug development against various diseases, including cancer and tuberculosis. Herein, we present an integrated approach combining in vitro biochemical assays with in silico molecular docking analysis to evaluate the inhibitory potential of 4-piperidine-based thiosemicarbazones 5(a-s) against DHFR. In our in vitro study, a novel series of 4-piperidine-based thiosemicarbazones 5(a-s) were assessed for their inhibitory activity against DHFR enzyme. The synthesized compounds 5(a-s) exhibited potent inhibition with IC50 values in the range of 13.70 ± 0.25 µM to 47.30 ± 0.86 µM. Among all the derivatives 5p displayed highest inhibitory activity. Simultaneously, in silico analysis were performed and compared with standard drug (Methotrexate) to predict the binding affinity and interaction pattern of synthesized compounds with DHFR active site. SAR analysis was done to elucidate how structural modifications impact compound's biological activity, guiding the rational design of potent and selective drug candidates for targeted diseases. These findings may provide a comprehensive assessment of 4-piperdine-based thiosemicarbazones as DHFR inhibitors and contribute to the development of novel therapeutics targeting DHFR-associated diseases.

Novel efficacy of pregnane and flavonoid glycosides from Desmidorchis flava in in vivo nociceptive and inflammatory paradigms and their target prediction by cheminformatics approach.

Inflammation is associated with multiple life-threatening conditions. Desmidorchis flava is an edible plant and traditionally used for managing various diseases. Three novel molecules, namely desmiflavaside-C (1), nizwaside (2), and desmiflanoside (3) were isolated from Desmidorchis flava, and their structures were confirmed by mass spectrometry and through reported literature. These compounds were in vivo examined for antinociceptive (tonic visceral nociception) and anti-inflammatory (carrageenan induced paw edema) activities. Significant antinociceptive potential was demonstrated by compound 1 at 0.5 and 1 mg/kg doses followed by compounds 2 and 3. At similar doses, significant anti-inflammatory activity was noted for all the tested compounds. Their antinociceptive and anti-inflammatory activities were comparable to the reference standards. In silico predicted binding modes suggests that these compounds may target allosteric sites of COX-1 and COX-2 enzymes to elicit their anti-inflammatory activities. These isolated natural products may have therapeutic potential in conditions afflicted with pain and inflammation.

Novel benzimidazole-based azine derivatives as potent urease inhibitors: synthesis, in vitro and in silico approach.

Aim: In light of various biological activities of benzimidazole and azines, this study focuses on reporting novel derivatives of benzimidazole nucleus.Methods: Twenty novel azines of benzimidazole were synthesized, characterized and tested for in vitro urease inhibitory activity.Results: All these derivatives showed excellent to good inhibition in the range of IC50 values 14.21 ± 1.87 to 76.11 ± 1.81 µM by comparing with standard thiourea 21.14 ± 0.42 µM. Docking studies were performed for the targeted benzimidazole derivatives to understand the binding mechanics. The results indicated higher binding efficacy compared with the reference inhibitor.Conclusion: This work identifies potential lead candidates for novel urease inhibitors, which with industrial support may be harnessed for the development of new drugs.

[Box: see text].

Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities.

Esophageal squamous cell carcinoma (ESCC) is a substantial global health burden. Immune escape mechanisms are important in ESCC progression, enabling cancer cells to escape the surveillance of the host immune system. One key player in this process is the Aryl Hydrocarbon Receptor (AhR), which influences multiple cellular processes, including proliferation, differentiation, metabolism, and immune regulation. Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis, epithelial-mesenchymal transition, and immune escape. Targeting AhR signaling is a potential therapeutic approach for ESCC, with AhR ligands showing efficacy in preclinical studies. Additionally, modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention. This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials.

Carbonic anhydrase II (CA II) is crucial for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance. It is a pivotal druggable target which is implicated in glaucoma, renal, gastric, and pancreatic carcinomas, as well as in malignant brain tumours. Therefore, to identify new CA II (bovine) inhibitors, the current study was designed to synthesize a library of 20 new triazole-linked hydrazones (6a-t). All compounds were characterized by using spectroscopic techniques such as NMR and mass spectrometry. The in-vitro evaluation resulted in impressive inhibitory capability against CA II with IC50 values ranging from 9.10 ± 0.26-48.26 ± 1.30 µM. Among all derivatives, compounds 6a, 6b, 6d, 6k-6m, 6q, 6s and 6t exhibited potent inhibitory potential with 6t deemed as the most active inhibitor. Additionally, kinetic study of the hybrid 6t revealed concentration dependent type of inhibition with Ki value 7.24 ± 0.0086 µM. Furthermore, molecular docking of 6t correlates well with the kinetic analysis. The in-silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development.

Exploring the aroma profile and biomedical applications of Scutellaria nuristanica Rech. F.: A new insight as a natural remedy.

BACKGROUND: The Scutellaria genus has promising therapeutic capabilities as an aromatherapy. Based on that and local practices of S. nuristanica Rech. F. The essential oil was studied for the first time for its diverse biomedical applications. PURPOSE: This study aimed to evaluate and validate their therapeutic capabilities by screening the essential oil ingredients and examining their antimicrobial, antioxidant, carbonic anhydrase, and antidiabetic using further In silico assessment and In vivo anti-inflammatory and analgesic capabilities to devise novel sources as natural remedies alternative to the synthetic drugs. METHODS: Essential oil was obtained through hydrodistillation, and the constituents were profiled using GC-MS. The antimicrobial assessment was conducted using an agar well diffusion assay. Free radical scavenging capabilities were determined by employing DPPH and ABTS assay. The carbonic anhydrase-II was examined using colorimetric assay, while the antidiabetic significance was performed using α-Glucosidase assay. The anti-inflammatory significance was examined through carrageenan-induced paw edema, and the analgesic features of the essential oil were determined using an acetic acid-induced writhing assay. RESULTS: Fifty constituents were detected in S. nuristanica essential oil (SNEO), contributing 95.93 % of the total EO, with the predominant constituents being 24-norursa-3,12-diene (10.12 %), 3-oxomanoyl oxide (9.94 %), methyl 7-abieten-18-oate (8.85 %). SNEO presented significance resistance against the Gram-positive bacterial strains (GPBSs), Bacillus atrophaeus and Bacillus subtilis, as compared to the Salmonella typhi and Klebsiella pneumoniae, Gram-negative bacterial strains (GNBSs) as well as two fungal strains Aspergillus parasiticus and Aspergillus niger associated with their respective standards. Considerable free radical scavenging capacity was observed in DPPH compared to the ABTS assay when correlated with ascorbic acid. In addition, when equated with their standards, SNEO offered considerable in vitro carbonic anhydrase II and antidiabetic capabilities. Additionally, the antidiabetic behavior of the 9 dominant compounds of SNEO was tested via In silico techniques, such as molecular docking, which assisted in the assessment of the significance of binding contacts of protein with each chemical compound and pharmacokinetic evaluations to examine the drug-like characteristics. Molecular dynamic simulations at 100 ns and binding free energy evaluations such as PBSA and GBSA models explain the molecular mechanics and stability of molecular complexes. It was also observed that SNEO depicted substantial anti-inflammatory and analgesic capabilities. CONCLUSION: Hence, it was concluded that the SNEO comprises bioactive ingredients with biomedical significance, such as anti-microbial, antioxidant, CA-II, antidiabetic, anti-inflammatory, and analgesic agents. The computational validation also depicted that SNEO could be a potent source for the discovery of anti-diabetic drugs.

Disrupting protease and deubiquitinase activities of SARS-CoV-2 papain-like protease by natural and synthetic products discovered through multiple computational and biochemical approaches.

The single-stranded RNA genome of SARS-CoV-2 encodes several structural and non-structural proteins, among which the papain-like protease (PLpro) is crucial for viral replication and immune evasion and has emerged as a promising therapeutic target. The current study aims to discover new inhibitors of PLpro that can simultaneously disrupt its protease and deubiquitinase activities. Using multiple computational approaches, six compounds (CP1-CP6) were selected from our in-house compounds database, with higher docking scores (-7.97 kcal/mol to -8.14 kcal/mol) and fitted well in the active pocket of PLpro. Furthermore, utilizing microscale molecular dynamics simulations (MD), the dynamic behavior of selected compounds was studied. Those molecules strongly binds at the PLpro active site and forms stable complexes. The dynamic motions suggest that the binding of CP1-CP6 brought the protein to a closed conformational state, thereby altering its normal function. In an in vitro evaluation, CP2 showed the most significant inhibitory potential for PLpro (protease activity = 2.71 ± 0.33 µM and deubiquitinase activity = 3.11 ± 0.75 µM), followed by CP1, CP5, CP4 and CP6. Additionally, CP1-CP6 showed no cytotoxicity at a concentration of 30 µM in the human BJ cell line.

Corrigendum to "Antimicrobial topical polymeric films loaded with Acetyl-11-keto-ß-boswellic acid (AKBA), boswellic acid and silver nanoparticles: Optimization, characterization, and biological activity" [Heliyon 10(11) 15th June 2024, e31671].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e31671.].

Synthesis, in vitro, and in silico study of novel pyridine based 1,3-diphenylurea derivatives as tyrosinase inhibitors.

Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a-t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC50 value of the inhibitors (15.78 µM) is lower than that of kojic acid (17.3 µM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC50 value of 3.5 ± 1.2  µM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders.